The present invention relates generally to the field of magnetic sensing, such as magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) spectroscopy. More particularly, the present invention relates to multi-well sample holders, such as assay plates, that are used in these processes. The multi-well sample holders are formed of a material having a magnetic susceptibility that is matched to the samples being analyzed. The present invention further relates to methods of performing high-throughput screening using magnetic sensing techniques.
Multi-well assay plates are used in a wide variety of high-throughput measurements in clinical chemistry and immunology, as well as in drug discovery and other research applications. Magnetic resonance imaging (MRI) of multi-well plates offers the possibility of performing new kinds of high-throughput assays, including the detection of targeted magnetic nanoparticles attached to analytes (e.g., located on or within cells). Moreover, MRI-guided localized nuclear magnetic resonance (NMR) spectroscopy could be used to perform high-throughput analyses of complex mixtures of chemicals not possible by any other common analytical technique. Best of all, conventional MRI techniques exist which could permit all samples in one or more multi-well plates to be analyzed simultaneously. However, conventional multi-well assay plates typically exhibit poor performance for MRI-based assays, since they provide inadequate matching of the magnetic susceptibility between the sample (e.g., the solvent and solute) and it surroundings. This results in complex distortion of the magnetic field around each sample, as well as between samples. This has undesirable effects, such as deteriorating the detection limit for magnetic nanoparticles, or rendering it impossible to resolve NMR spectra for individual samples. As a result of these and other drawbacks associated with conventional multi-well assay plates, high-throughput analysis using some types of magnetic analysis (e.g., chemical analysis using localized NMR) has been impractical or impossible. For example, it has been difficult or impossible to obtain NMR spectra directly from individual wells of a multi-well plate (i.e., without transferring the contents of each well to one or more NMR tubes or flow cells).
What is needed, therefore, is a multi-well sample holder and related methods that overcome the shortcomings of the prior art offerings, such as, the reduction in sensitivity, resolution, and signal-to-noise ratio caused by the inhomogeneities of the magnetic field that result from susceptibility variations when using conventional sample holders.